The understanding of adhesive interaction at the nanoscale between functionalized nanoparticles and biological cells is of great importance to develop effective theranostic nanocarriers for targeted cancer therapy. Here, we report a combination of experimental and computational approaches to evaluate the adhesion between Triptorelin (a Luteinizing Hormone-Releasing Hormone (LHRH) agonist)-conjugated poly-(ethylene glycol) (PEG)-coated magnetite nanoparticles (Triptorelin-MNPs) and breast cells. The adhesion forces between Triptorelin-MNPs and normal/cancerous breast cells are obtained using atomic force microscopy...

Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of "molecular mimicry". In this paper we propose and analyse a stochastic model of immune response to a viral infection and subsequent autoimmunity, with account for the populations of T cells with different activation thresholds, regulatory T cells, and cytokines. We show analytically and numerically how stochasticity can result in sustained oscillations around deterministically stable steady states, and we also investigate stochastic dynamics in the regime of bi-stability...

The developing neocortex in the mammalian brain is composed of multiple cell types including apical progenitors (AP), basal progenitors (BP), and neurons that populate three different layers, the ventricular zone (VZ), the subventricular zone (SVZ), and the cortical plate (CP). Despite recent advances, the diversity of the existing cell populations including those which are differentiating and mature, their biogenesis and the underlying gene regulatory mechanisms remain poorly known. Recent studies have taken advantage of the rapidly emerging single-cell technologies to decode the heterogeneity of cell populations at the transcriptome level during cortical development and their molecular details...

Is it possible to recover the position of a source from the steady-state fluxes of Brownian particles to small absorbing windows located on the boundary of a domain? To address this question, we develop a numerical procedure to avoid tracking Brownian trajectories in the entire infinite space. Instead, we generate particles near the absorbing windows, computed from the analytical expression of the exit probability. When the Brownian particles are generated by a steady-state gradient at a single point, we compute asymptotically the fluxes to small absorbing holes distributed on the boundary of half-space and on a disk in two dimensions, which agree with stochastic simulations...

By virtue of their regulatory role in the biological process, certain protein-protein complexes form potential targets for designing and discovery of drugs. Alteration set in the controlled formation of such complexes results in dysregulation of several metabolic processes, leading to diseased condition. β-catenin/Tcf4 complex is one such protein-protein complex found altered in colorectal epithelial cells resulting in activation of target genes leading to cancer. Recently certain lignans from seeds of the oil crop sesame were found inhibiting initiation and progression of this type of cancer...

Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation...

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...

The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX 2 R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX 2 R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX 2 R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX 2 R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM and MMGBSA calculations...

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD19, CD20 and CD52 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...

Ubiquitin-binding proteins play an important role in eukaryotes by translating differently linked polyubiquitin chains into proper cellular responses. Current knowledge about ubiquitin-binding proteins and ubiquitin linkage-selective interactions is mostly based on case-by-case studies. We have recently reported a method called ubiquitin interactor affinity enrichment-mass spectrometry (UbIA-MS), which enables comprehensive identification of ubiquitin interactors for all ubiquitin linkages from crude cell lysates...

Quantifying cell morphology is fundamental to the statistical study of cell populations, and can help unravel mechanisms underlying cell and tissue morphogenesis. Current methods, however, require extensive human intervention, are highly parameter sensitive, or produce metrics difficult to interpret biologically. We therefore developed a method, Lobe Contribution Elliptical Fourier Analysis (LOCO-EFA), which generates from digitalised 2D cell outlines meaningful descriptors that can be directly matched to morphological features...

We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses...

Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation...

Novel slim and shapely sp3-rich nitrogen containing heterocyclic ring systems are sought-after platforms for the expansion of molecular diversity in lead discovery. The present work describes the synthesis and characterization of a series of derivatives of hitherto unknown 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines 2. This approach was guided by a computational study, aiming at an optimization of previously reported [1,2,4]triazolo[1,2-a]pyridazine-1-thiones 1 known to inhibit the inducible nitric oxide synthase (iNOS)...

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome. DESIGN: We developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome...

BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology...

PURPOSE: Prognostic biomarkers are needed to guide the management of early-stage non-small cell lung cancer (NSCLC). This work aims to develop an image-based prognostic signature and assess its complementary value to existing biomarkers. METHODS AND MATERIALS: We retrospectively analyzed data of stage I NSCLC in 8 cohorts. On the basis of an analysis of 39 computed tomography (CT) features characterizing tumor and its relation to neighboring pleura, we developed a prognostic signature in an institutional cohort (n = 117) and tested it in an external cohort (n = 88)...

Cryogenic transmission electron microscopy (cryo-TEM) is a high-resolution biological imaging method, whereby biological samples, such as purified proteins, macromolecular complexes, viral particles, organelles and cells, are embedded in vitreous ice preserving their native structures. Due to sensitivity of biological materials to the electron beam of the microscope, only relatively low electron doses can be applied during imaging. As a result, the signal arising from the structure of interest is overpowered by noise in the images...

Hundreds and hundreds of bacterial protein toxins are presently known. Traditionally, toxin identification begins with pathological studies of bacterial infectious disease. Following identification and cultivation of a bacterial pathogen, the protein toxin is purified from the culture medium and its pathogenic activity is studied using the methods of biochemistry and structural biology, cell biology, tissue and organ biology, and appropriate animal models, supplemented by bioimaging techniques. The ongoing and explosive development of high-throughput DNA sequencing and bioinformatic approaches have set in motion a revolution in many fields of biology, including microbiology...

Recent studies have shown that cell cycle and cell volume are confounding factors when studying biological phenomena in single cells. Here we present a combined experimental and computational method, CellCycleTRACER, to account for these factors in mass cytometry data. CellCycleTRACER is applied to mass cytometry data collected on three different cell types during a TNFα stimulation time-course. CellCycleTRACER reveals signaling relationships and cell heterogeneity that were otherwise masked.